Computational affinity maturation of camelid single-domain intrabodies against the nonamyloid component of alpha-synuclein.

ABSTRACT: Improving the affinity of protein-protein interactions is a challenging problem that is particularly important in the development of antibodies for diagnostic and clinical use. Here, we used structure-based computational methods to optimize the binding affinity of V_HNAC1, a single-domain intracellular antibody (intrabody) from the camelid family that was selected for its specific binding to the nonamyloid component (NAC) of human α-synuclein (α-syn), a natively disordered protein, implicated in the pathogenesis of Parkinson's disease (PD) and related neurological disorders. Specifically, we performed ab initio modeling that revealed several possible modes of V_HNAC1 binding to the NAC region of α-syn as well as mutations that potentially enhance the affinity between th

SUBMITTER: Mahajan SP 

PROVIDER: S-EPMC6279780 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature